Poster Presentation First Malaria World Congress 2018

Characterisation of gametocyte-specific antibodies in sera from malaria-infected individuals to identify the functional determinants of transmission blocking immunity (#456)

Siddhartha Mahanty 1 , David Grimson 1 , Christelle Buffet 1 , James Beeson 2 , Matthew Dixon 1 , Stephen Rogerson 1
  1. The University of Melbourne, Melbourne, VIC, Australia
  2. Malaria Research: Immunity, Vaccines and New Therapies Laboratory, The Burnet Institute, Melbourne, VIC, Australia

Transmission of Plasmodium falciparum (Pf) from the human host to the mosquito vector is a complex process involving the sexual stages of the parasite that include gametocytes (Gam).  Antibodies (Abs) targeting some antigens (Ags) expressed in these stages generate transmission blocking immunity (TBI) that can inhibit parasite growth and interrupt malaria transmission.  However, the mechanisms through which antibodies inhibit transmission to mosquitoes, and the specific antigenic targets, are not well understood.   Our goal is to identify the functional properties of Abs and specific antigen targets associated with TBI.  We screened pre-treatment sera from 306 pregnant adults in Papua New Guinea who were enrolled in a malaria treatment study, for prevalence of Abs against a model Gam-associated Ag known to possess TB activity, Pfs230.  Sixty three percent (192/306) of sera from this cohort had IgG Abs against a recombinant (23kD) fragment of Pfs230 by ELISA. In a subset of individuals with anti-Pfs230 IgG, Ag-specific IgG1 was detected in 89%, IgG2 in 34% and IgG3 in 18% of sera tested.  Immunofluorescence assays using in vitro cultured gametocytes (laboratory-adapted 3D7 parasites) co-localised the anti-Gam IgG present in 3 human sera with antibodies specific for Pfs230 (on parasite plasma membrane), PHIL1 (on the inner membrane complex) and Pfs16 (a parasitophorous vacuole protein), but also recognised many other targets on Gams.  Western blot analysis of these sera using extracts of Gams as Ags identified a number of targets. Characterisation of anti-Gam IgG from infected individuals is ongoing to determine the biophysical and functional properties of anti-gametocyte antibodies that best correlate with TBI. A better understanding of the mechanisms of transmission blocking immunity will facilitate the development of vaccines aimed at blocking transmission.